Tannic acid attenuates vascular calcification-induced proximal tubular cells damage through paracrine signaling - 17/06/21
pages | 12 |
Iconographies | 6 |
Vidéos | 0 |
Autres | 0 |
Abstract |
Vascular calcification is common in chronic kidney disease; however, the extent to which such condition can affect the renal microvasculature and the neighboring cell types is unclear. Our induced-calcification model in renal proximal tubular (PT) cells exhibited endoplasmic reticulum (ER) stress and oxidative damage, leading to apoptosis. Here, we utilized such calcification in mouse vascular smooth muscle (MOVAS-1) cells as a vascular calcification model, because it exhibited reactive oxygen species (ROS) generation, ER and oxidative stress, inflammatory, and apoptotic gene expressions. To demonstrate whether the vascular calcification condition can dictate the function of the adjacent PT cell layer, we utilized a Transwell multilayer culture system by combining those MOVAS-1 cells in the bottom chamber and polarized PT cells in the upper chamber to show the dimensional cross-signaling effect. Interestingly, calcification of MOVAS-1 cells, in this co-culture, induced H2O2 and lactate dehydrogenase (LDH) release leading to store-operated Ca2+ entry, ROS generation, and activation of oxidative, inflammatory, and apoptotic gene expressions in PT cells through paracrine signaling. Interestingly, application of tannic acid (TA) to either calcified MOVAS-1 or uncalcified PT cells diminished such detrimental pathway activation. Furthermore, the TA-mediated protection was much higher in the PT cells when applied on the calcified MOVAS-1 cells, and the delayed the pathological effects in neighboring PT cells can well be via paracrine signaling. Together, these results provide evidence of vascular calcification-induced PT cell damage, and the protective role of TA in preventing such pathological consequences, which can potentially be used as a nephroprotective remedy.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Schematic diagram of dissected kidney showing microvasculature (left) which is replicated in a simplified model with multicellular Transwell system. Enlarged showing proximal tubular (PT) cells (lower right) in response to vascular calcification, causing the release of H2O2, which induce store-operated Ca2+ entry (SOCE), leading to endoplasmic reticulum (ER) stress and oxidative damage. Application of Tannic acid (lower left) abrogated such ER and oxidative stress induced cell death by lower the SOCE. Tight Junction (TJ).
Highlights |
• | Modelling vascular calcification by ROS activation in calcium crystal-ingested vascular smooth muscle cells (MOVAS-1). |
• | Proximal tubular (PT)/MOVAS-1 cells in transwell co-culture to study tubular/vascular calcification induced cross-signaling. |
• | Store-operated Ca2+ entry in PT cells due to vascular calcification as functional crosstalk and its block by Tannic acid. |
• | Protection against vascular calcification-induced PT cell damage by tannic acid via paracrine signaling. |
• | Tannic acid delayed the pathological effects of vascular calcification in neighboring PT cells via anti-ROS mechanism. |
Abbreviations : BAX1, XBP-1, MCP1, CKD, PT, CaP, CaNL, ROS, VSMC, ER, TA, HK2, GRP78, PM, 2-APB, LDH, GPX, FMO2, NOX, IL, NLRP, CHOP, NFκβ, SOCE, Fura-2AM
Keywords : Renal microvasculature, Calcification, Proximal tubule, Oxidative stress, LDH release, Cell communication, Paracrine signaling, Tannic acid
Plan
Vol 140
Article 111762- août 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?